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Study on IOP-independent glaucoma treatment and pathogenetic mechanisms of glaucomatous optic neuropathy

Research Project

Project/Area Number 11470362
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Ophthalmology
Research InstitutionGifu University

Principal Investigator

SUGIYAMA Kazuhisa (2000-2001)  Gifu University, School of Medicine, Associate Professor, 医学部, 助教授 (80179168)

北澤 克明 (1999)  岐阜大学, 医学部, 教授 (20009484)

Co-Investigator(Kenkyū-buntansha) KAWASE Kazuhide  Gifu University, School of Medicine, Assistant professor, 医学部・附属病院, 講師 (40234067)
TANIGUCHI Toru  Gifu University, School of Medicine, Assistant professor, 医学部・附属病院, 講師 (30179840)
YAMAMOTO Tetsuya  Gifu University, School of Medicine, Professor, 医学部, 教授 (50134581)
UCHIDA Hideya  Gifu University, School of Medicine, Assistant professor, 医学部・附属病院, 講師 (70273133)
杉山 和久  岐阜大学, 医学部・附属病院, 講師 (80179168)
富田 剛司  東京大学, 医学部, 助教授 (30172191)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥6,800,000 (Direct Cost: ¥6,800,000)
Keywordsglaucoma / optic neuropathy / neuroprotection / calcium-channel blocker / NMDA受容体阻害薬 / 二酸化炭素
Research Abstract

We first established two experimental models of glaucomatous optic neuropathy: one by intracameral Indian ink injection followed by laser irradiation to the chamber angle and the other by direct optic nerve damage with a clip. Using the models, several kinds of drugs were investigated in terms of possible neuroprotective effect on glaucomatous.optic neuropathy. Noncompetitive NMDA receptor antagonists, T-588, tacrolimus and betaxolol successfully showed neuroprotective effects on the models, which were confirmed by retinal ganglion cell counts, histopathology and electroretinogram measurement. These results suggest the possibility of IOP-independent glaucoma therapy by pharmacological modification of the apoptotic process.
Another rat model for retinal ganglion cell apoptosis was created by thrombosis formation and reperfusion of the retinal arteries. Time-dependent apoptotic reaction was observed in the model, suggesting that the model might be used for investigation of glaucomatous optic neuropathy.
We investigated lOP-independent factors for development and progression of glaucomatous optic neuropathy in a clinical setting. A multivariate analysis demonstrated several lOP-independent factors such as optic disc hemorrhage, peripapillary atrophy and abnormal orbital hemodynamics were associated with progression of glaucomatous optic neuropathy. Calcium-channel blocker treatment was associated with favorable prognosis of optic neuropathy.
These results indicate the possibility of totally new treatment modalities for glaucoma other than currently used ocular hypotensive therapy.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report

Research Products

(56 results)

All Other

All Publications (56 results)

  • [Publications] Niwa Y.: "A new system to supply carbon dioxide safely to glaucoma patients"Japanese Journal of Ophthalmology. 43(1). 16-19 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uchida H.: "Peripapillary atrophy in primary angle-closure glaucoma : a comparative study with primary open-angle glaucoma"American Journal of Ophthalmology. 127(2). 121-128 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Daugeline L.: "Risk factors for visual field damage progression in normal-tension glaucoma eyes"Graefes Arch Clin Exp Ophthalmol. 237. 105-108 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto T.: "Role of trabeculectomy and calcium-channel blockers in the treatment of normal-tension glaucoma"Glaucoma. 6. 163-166 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kitazawa Y.: "Disc hemorrhage as a risk factor for progression of normal-tension glaucoma"Pathogesis and Risk Factors of Glaucoma. 145-154 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto T.: "Prevalence of normal-tension glaucoma and primary openangle glaucoma in patients with collagen diseases"Japanese Journal of ophthalmology. 43(6). 539-542 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiyama K.: "Optic nerve and peripapillary choroidal microvasculature of the rat eye"Investigative Ophthalmology & Vis Sci. 40(13). 3084-3090 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 谷 照斌: "ラット実験的緑内障眼におけるN-メチル-D-アスパラギン酸受容体阻害薬の神経保護作用の検討"日本眼科学会雑誌. 104(1). 11-16 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niwa Y.: "Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glaucoma"Journal of Glaucoma. 9(3). 262-267 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishida K.: "Disk haemorrhage is a significantly negative, prognostic factor in normal-tension glaucoma"American Journal of Ophthalmology. 129(6). 707-714 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Daugeline L: "Transient ischemic in jury in the rat retina caused by thrombotic occlusion-thrombolytic reperfusion"Investigative Ophthalmology & Vis Sci.. 41(9). 2743-2747 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomita G.: "Changes in optic nerve head blood flow and retrobulbar hemodynamics following calcium-channel blocker treatment of normaltension glaucoma"Int Ophthalmology. 23. 3-10 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kondo Y.: "Retrobulbar hemodynamics in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure"American Journal of Ophthalmology. 23. 454-460 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiyama K.: "Disk haemorrhages in normal-tension glaucoma"Asian J Ophthalmol. 2(3). 3-8 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 山本哲也: "正常眼圧緑内障に対する治療の有効性と限界"臨床眼科. 54(12). 1757-1761 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki Y.: "Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma"Journal of Glaucoma. 10(2). 121-128 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamada Y.: "Intraocular Pressure-lowering efficacy of latanoprost in patients with normal-tension glaucoma or primary open-angle glaucoma"J Ocul Pharmacol Ther. 17(1). 19-25 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liou S: "Morphometric characteristics of optic disc with disc haemorrhage in normal-tension glaucoma"American Journal of Ophthalmology. 132(5). 618-625 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 高橋慎一: "乳頭出血の既往の有無による正常眼圧緑内障眼底の網膜血管血流の比較"日本眼科学会雑誌. 105(3). 177-182 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 山本哲也: "緑内障性視神経症に対する神経保護的治療の黎明"日本眼科学会雑誌. 105(12). 866-883 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niwa,Y., Harris,A., Kagemann,LE., Yamamoto,T., Matsubara,M., Takahashi,D., Kitazawa,Y.: "A new system to supply carbon dioxide safely to glaucoma patients"Jpn J Ophthalmol. 43 ( l ). 16-19 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Uchida,H., Yamamoto,T., Tomita,G., Kitazawa,Y.: "Peripapillary atrophy in primary angle-closure glaucoma: a comparative study with primary open-angle glaucoma"Peripapillary atrophy in primary angle-closure glaucoma: a comparative study with primary open-angle glaucoma. 127 ( 2 ). 121-128 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Daugeliene,L., Yamamoto,T., Kitazawa,Y.: "Risk factors for visual field damage progression in normal-tension glaucoma eyes"Graefes Arch Clin Exp Ophthalmol. 237. 105-108 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto,T., Kitazawa,Y., Ishida,K., Daugeliene,L.: "Role trabeculectomy and calcium-channel blockers in the treatment of normal-tension glaucoma"Glaucoma Update Vol VI. Ed by Krieglstein GK p163-166 Springer Verlag, Heidelberg, Germany. VI. 163-166 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kitazawa,Y., Yamamoto,T., Ishida,K.: "Disc hemorrhage as a risk factor for progression of normal-tension glaucoma"Pathogenesis and Risk Factors of Glaucoma. Ed by Gramer E & Grehn F p145-154 Springer Verlag, Heidelberg, Germany. 145-154 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto,T., Maeda,M., Sawada,A., Sugiyama,K., Taniguchi,T., Kitazawa,Y., Oyama,Z., Ichihashi,N., Takagi,H., Kitajima,Y.: "Prevalence of normal-tension glaucoma and primary open-angle glaucoma in patients with collagen diseases"Jpn J Ophthalmol. 43 ( 6 ). 539-542 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiyama,K., Gu,ZB., Kawase,C., Yamamoto,T., Kitazawa,Y.: "Optic nerve and peripapillary choroidal microvasculature of the rat eye"Invest Ophthalmol Vis Sci. 40 ( 13 ). 3084-3090 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Gu,ZB., Yamamoto,T., Kawase,C., Matsubara,M., Kawase,K., Sawada,A., Kitazawa,Y.: "Neuroprotective effect of N-methyl-D-aspartate receptor antagonists in an experimental glaucoma model in the rat"J Jpn Ophthalmol Soc. 104 ( 1 ). 11-16 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Niwa,Y., Yamamoto,T., Harris,A., Kagemann,L., Kawakami,H., Kitazawa,Y.: "Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glaucoma"J Glaucoma 9 ( 3 ). 262-267 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ishida,K., Yamamoto,T., Sugiyama,K., Kitazawa,Y.: "Disk hemorrhage is a significantly negative, prognostic factor in normal-tension glaucoma"Am J Ophthalmol. 129 ( 6 ). 707-714 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Daugeliene,L., Niwa,M., Kara,A., Matsuno,H., Yamamoto,T., Kitazawa,Y., Uematsu,T.: "Transient ischemic injury in the rat retina caused by thrombotic occlusion-thrombolytic reperfusion"lnvest Ophthalmol Vis Sci. 41 ( 9 ). 2743-2747 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tomita,G., Niwa,Y., Shinohara,H., Yamamoto,T., Kitazawa,Y.: "Changes in optic nerve head blood flow and retrobulbar hemodynamics following calcium-channel blocker treatment of normal-tension glaucoma"lnt Ophthalmol. 23. 3-10 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kondo,Y., Niwa,Y., Yamamoto,T., Sawada,A., Harris,A., Kitazawa,Y.: "Retrobulbar hemodynamics in normal-tension glaucoma with asymmetric visual field change and asymmetric ocular perfusion pressure"Am J Ophthalmol. 130 ( 2 ). 454-460 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sugiyama,K., Ishida,K., Uchida,H., Yamamoto,T., Kitazawa,Y.: "Disc haemorrhages in normal tension glaucoma"Asian J Ophthalmol. 2 ( 3 ). 3-8 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto,T.: "Contemporary treatment of normal-tension glaucoma"Rinshoganka. 54 ( 12 ). 1757-1761 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki,Y., Kitazawa,Y., Araie,M., Yamagami,J., Yamamoto,T., Ishida,K., Tsuji,A., Abe,H., Shirakashi,M., Funaki,S., Mishima,HK., Tsukamoto,H., Okada,K., Shibata,T.: "Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma"J Glaucoma. 10 ( 2 ). 121-128 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tamada,Y., Taniguchi,T., Murase,H., Yamamoto,T., Kitazawa,Y.: "Intraocular pressure-lowering efficacy of latanoprost in patients with normal-tension glaucoma or primary open-angle glaucoma"J Ocul Pharmacol Ther. 17 ( 1 ). 19-25 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Liou,S., Sugiyama,K., Uchida,H., Gu,ZB., Yamamoto,T., Tomita,G., Kitazawa,Y.: "Morphometric characteristics of optic disk with disk hemorrhage in normal-tension glaucoma"Am J Ophthalmo. 132 ( 5 ). 618-625 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takahashi,S., Tomita,G., Sugiyama,K., Sato,Y., Kitazawa,Y.: "Blood flow in retinal vessels of normal-tension glaucoma with or without a history of optic disc hemorrhages"J Jpn Ophthalmol Soc. 105 ( 3 ). 177-182 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto,T.: "The dawn of neuroprotective therapy for glaucomatous optic neuropathy"J Jpn Ophthalmol Soc. 105 ( 12 ). 866-883 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Suzuki Y: "Mathematical and optimal clustering of test points of the central 30-degree visual field of glaucoma"Journal of Glaucoma. 10・2. 121-128 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Tamada Y: "Intraocular pressure-lowering efficacy of latanoprost in patients with normal-tension glaucoma or Primary open-angle glaucoma"J.Ocul. Pharmacol Ther. 17・1. 19-25 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Lios S: "Morphometric characteristics of optic disk with disk nemorrhage in normal-tension glaucoma"American Journal of Ophthalmology. 132・5. 618-625 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋 慎一: "乳頭出血の既往の有無による正常眼圧緑内障眼底の網膜血管血流の比較"日本眼科学会雑誌. 105・3. 177-182 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 山本 哲也: "緑内障性視神経症に対する神経保護的治療の黎明"日本眼科学会雑誌. 105・12. 866-883 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 谷照斌: "ラット実験的緑内障眼におけるN-メチル-D-アスパラギン酸受容体阻害薬の神経保護作用の検討"日本眼科学会雑誌. 104・1. 11-16 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Niwa Y: "Relationship between the effect of carbon dioxide inhalation or nilvadipine on orbital blood flow in normal-tension glow corr"Journal of Glaucoma. 9・3. 262-267 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ishido K: "Disk hemorrhage is a significantly negative, prognostic factor in normal-tension glaucoma."American Journal of Ophthalmology. 129・6. 707-714 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Daugeliene L: "Transient ischemic injury in the rat retina caused by thrombotic occlusion-thrombolytic reperfu"Investigative Ophthalomology and Visual Science. 41・9. 2743-2747 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tomita G: "Changes in optic nerve head blood flow and retrobulbar hemodynamics following calcium-channel blocker treatment of normal-tension glancoma."International of Ophthalmology. 23. 3-10 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 山本哲也: "正常眼圧緑内障に対する治療の有効性と限界"臨床眼科. 54・12. 1757-1761 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yamamoto T.: "Role of trabeculectomy and calcium-channel blockers in the treatment of nornal-tension glaucoma"Glaucoma Update Vol VI. 163-166 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitazawa Y.: "Disk hemorrhage as a risk factor for progression of normal-tension glaucoma"Pathogenesis and Risk Factors of Glaucoma. 145-154 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kitazawa Y.: "Calcium channel blockers and ocular blood flow in normal-tension glaucoma"Current Concepts on Ocular Blood Flow in Glaucoma. 235-240 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sugiyama K.: "Optic nerve and peripapillary choroidal microvasculature of the rat eye."Investigative Ophthalmology and Visual Science. 40・13. 3084-3090 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷照斌: "ラット実験的緑内障眼におけるN-メチル-D-アスパラギン酸受容体阻害薬の神経保護作用の検討"日本眼科学会雑誌. 104・1. 11-16 (2000)

    • Related Report
      1999 Annual Research Report

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Published: 1999-03-31   Modified: 2016-04-21  

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